Single nucleotide polymorphisms in the gene encoding the protein tyrosine phosphatase TCPTP (encoded by PTPN2) have been linked with the development of autoimmunity. Here we have used Cre/LoxP recombination to generate Ptpn2ex2-/ex2- mice with a global deficiency in TCPTP on a C57BL/6 background and compared the phenotype of these mice to Ptpn2-/- mice (BALB/c-129SJ) generated previously by homologous recombination and backcrossed onto the BALB/c background. Ptpn2ex2-/ex2- mice exhibited growth retardation and a median survival of 32 days, as compared to 21 days for Ptpn2-/- (BALB/c) mice, but the overt signs of morbidity (hunched posture, piloerection, decreased mobility and diarrhoea) evident in Ptpn2-/- (BALB/c) mice were not detected in Ptpn2ex2-/ex2- mice. At 14 days of age, bone development was delayed in Ptpn2-/- (BALB/c) mice. This was associated with increased trabecular bone mass and decreased bone remodeling, a phenotype that was not evident in Ptpn2ex2-/ex2- mice. Ptpn2ex2-/ex2- mice had defects in erythropoiesis and B cell development as evident in Ptpn2-/- (BALB/c) mice, but not splenomegaly and did not exhibit an accumulation of myeloid cells in the spleen as seen in Ptpn2-/- (BALB/c) mice. Moreover, thymic atrophy, another feature of Ptpn2-/- (BALB/c) mice, was delayed in Ptpn2ex2-/ex2- mice and preceded by an increase in thymocyte positive selection and a concomitant increase in lymph node T cells. Backcrossing Ptpn2-/- (BALB/c) mice onto the C57BL/6 background largely recapitulated the phenotype of Ptpn2ex2-/ex2- mice. Taken together these results reaffirm TCPTP's important role in lymphocyte development and indicate that the effects on morbidity, mortality, bone development and the myeloid compartment are strain-dependent. © 2012 Wiede et al.
CITATION STYLE
Wiede, F., Chew, S. H., van Vliet, C., Poulton, I. J., Kyparissoudis, K., Sasmono, T., … Tiganis, T. (2012). Strain-dependent differences in bone development, myeloid hyperplasia, morbidity and mortality in Ptpn2-deficient mice. PLoS ONE, 7(5). https://doi.org/10.1371/journal.pone.0036703
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